Calcium signaling and c-fos gene expression via mg muscarinic acetylcholine receptors in human T- and B-cells
Calcium signaling and c-fos gene expression via mg muscarinic acetylcholine receptors in human T- and B-cells
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DOI：
10.1254/jjp.84.124
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发表时间：
2000-10-01
期刊：
影响因子：
--
通讯作者：
Kawashima, K
中科院分区：
文献类型：
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作者：
Fujii, T;Kawashima, K
我们之前的研究表明，血液中乙酰胆碱（ACh）主要来源于T淋巴细胞，刺激毒菌碱ACh受体（mAChRs）诱导Ca2+振荡，上调T淋巴细胞和b淋巴细胞中c-fos基因的表达。在本研究中，我们研究了人类T- (CEM)和B- (Daudi)细胞中哪些mAChR亚型参与Ca2+信号传导和c-fos基因表达。在两种细胞系中，用100 μ m的M-1/M-3激动剂oxotremorine-M刺激mAChRs，增加细胞内游离Ca2+ ([Ca2+](i))水平和c-fos mRNA表达。4-DAMP是一种M-3受体拮抗剂，它比m -1受体拮抗剂吡renzepine和telenzepine更有效地阻断oxotremorine- m诱导的[Ca2+](i)的增加；AF-DX 116，一种M-2拮抗剂；弱M-3拮抗剂六氢硅二苯醚醇；或者六甲铵和d-烟碱，它们都是尼古丁受体拮抗剂。McN-A-343 （100 muM）是一种部分m -1受体激动剂，在两种细胞系中对[Ca2+](i)均无明显影响。4-DAMP能抑制氧tremorine- m诱导的c-fos转录上调，而吡仑氮平和AF-DX 116则不能。因此，我们的研究结果表明，从T淋巴细胞释放的ACh作为自分泌/旁分泌因子，通过M-3受体将Ca2+依赖信号传递到T淋巴细胞和b淋巴细胞的细胞核。
We previously showed that blood acetylcholine (ACh) originates mainly from T-lymphocytes, and that stimulation of muscarinic ACh receptors (mAChRs) induces Ca2+ oscillations and up-regulates c-fos gene expression in both T- and B-lymphocytes. In the present study, we investigated which mAChR subtypes are involved in Ca2+ signaling and c-fos gene expression in human T- (CEM) and B- (Daudi) cells. Stimulation of mAChRs with 100 muM oxotremorine-M, an M-1/M-3 agonist, increased levels of intracellular free Ca2+ ([Ca2+](i)) and c-fos mRNA expression in both cell lines. 4-DAMP, an M-3 antagonist, more effectively blocked the oxotremorine-M-induced increase in [Ca2+](i) than pirenzepine and telenzepine, M-1-receptor antagonists; AF-DX 116, an M-2 antagonist; hexahydrosiladifenidol, a weak M-3 antagonist; or hexamethonium and d-tubocurarine, nicotinic receptor antagonists. McN-A-343 (100 muM), a partial M-1-receptor agonist, had no apparent effect on [Ca2+](i) in either cell line. The oxotremorine-M-induced up-regulation of c-fos transcription was inhibited by 4-DAMP, but not by pirenzepine or AF-DX 116. Our findings thus suggest that ACh released from T-lymphocytes acts as an autocrine/paracrine factor, transmitting a Ca2+-dependent signal to the nuclei of T- and B-lymphocytes via M-3 receptors.